Beta-Adrenergic receptors (Beta-ARs) modulate a variety of physiological responses, including the regulation of heart rate, smooth muscle contraction, gluconeogenesis and lipolysis. Three Beta-ARs (Betal-AR, Beta2-AR, and Beta3-AR) have been cloned, but data suggest that these three subtypes to do not account for all of the known physiological responses. Recent cloning of a novel avian Beta-AR in our lab (submitted for publication) further supports the evidence suggesting the existance of other Beta-ARs. In this project the novel avian Beta-AR gene (Beta4c- AR) will be used as a probe to screen a human genomic library at low stringency hybridization conditions in order to clone the human homologue of Beta4c-AR. Preliminary data from Southern hybridization analysis demonstrate that the Beta4c-AR probe hybridizes to human genonic DNA fragments that are different from those hybridized with a Beta2-AR and Beta3-AR probes. Clones obtained from the library will be analyzed by restriction enzyme fragment analysis and screened with Betal-AR, Beta2-AR, and Beta3-AR probes. Candidates of atypical Beta-ARs will be subcloned and sequenced. Sequences consistent with Beta-ARs will be expressed in COS cells and assessed for [125-Iliodocyanopindolol binding (a Beta-AR-specific antagonist). Ultimately pharmacological characterization and signal transduction mechanisms will be determined in the human homologue of Beta4c-AR .

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Unknown (K16)
Project #
5K16DE000165-14
Application #
6104549
Study Section
Project Start
1999-07-01
Project End
2000-06-30
Budget Start
Budget End
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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